The research proposed here would investigate cellular interactions involved in the immune response to viruses and viral antigens. An analysis of the development of the host defense against viruses and the cell types involved should allow insight into the natural response to these antigens and the possibility of manipulating that response. The cytotoxic T lymphoctye (CTL) has been shown to be important in the host response to infection in mice. These T cells are capable of lysing infected target cells which are identical at some region of the major histocompatibility complex (H-2 in the mouse). Certain cytotoxic T cell responses have been shown to be dependent upon helper T cells for their generation. In addition, these responses are influenced by suppressor T cells and are under the influence of Immune Response (IR) genes which affect the specificity and magnitude of the cytotoxic response. Examining the presentation of specific viral antigens in terms of their T cell-T cell associations, especially as they relate to the genetic restrictions seen in this system, should allow dissection in some of the crucial cell-cell and antigen-cell interactions involved in the host response to viruses and in Ir gene controlled immune responses in general. By utilizing systems in which single viral and host proteins can be examined in the context of host defenses, the significance of various cell regulatory and antigen-receptor interactions can be evaluated.